Abstract: Allergies affect over one third of the world's population, and the prevalence of asthma is estimated at 300 million patients worldwide 17. In the US alone, asthma prevalence is 8-10% with a subset of 10% who suffer from severe disease. Allergen-specific IgE is a major mediator of severe allergic conditions and asthma exacerbations, but little is understood about the biology of human IgE in these patients. The presence of human IgE long-lived plasma cells is a matter of controversy, since mouse models show little evidence of IgE BM resident plasma cells fueling debate that IgE levels are maintained only by ongoing replenishment from short-lived ASC. In my laboratory, we have identified a new LLPC subset in the human bone marrow (BM) compartment and characterized 5 novel circulating ASC populations. In this application, we will demonstrate the presence of human IgE BM LLPC in allergic patients and understand the cellular origins of allergen-specific IgE responses during acute recall responses (after natural allergen exposures) in blood, bone marrow and nasal polyps.